Currently and traditionally, defects in the bladder and other urothelial structures have been corrected surgically following cystectomy procedures. Some of the closure techniques following cystectomy involve auto augmentation for closure of the opening for which there is insufficient tissue or when the structure itself is deformed or too small to have complete closure and sufficient regeneration. The gold standard for the reconstruction of the bladder is enterocystoplasty, a procedure that uses intestinal bowel segments, however, this procedure is associated with several complications. Bowel segments have been used in reconstruction of genitourinary structures in these circumstances. The use of bowel in genitourinary reconstruction is associated with a variety of complications, including metabolic abnormalities, infection, perforation, urolithiasis, increased mucus production and malignancy.
Several materials, both absorbable and synthetic, have been used unsuccessfully as substitutes for the bowel segment in this reconstruction process for bladder repair/augmentation and regeneration. However no material has proven to be an ideal biomaterial for bladder reconstruction. Synthetic materials such as polyvinyl sponge, gelatin sponge, polytetrafluoroethylene, and silicon have been used unsuccessfully due to mechanical, structural or biocompatibility issues. Naturally derived materials such as dura, de-epithelialized bowel segment, omentum, peritoneum, seromuscular grafts, and small intestinal submucosa (SIS) have also been evaluated for bladder repair and replacement with limited success.
Recent studies indicate that the biodegradable polyester polymers made of polyglycolic acid are useful for bladder repair and reconstruction, as described by Vacanti, et al Selective cell transplantation using bioabsorbable artificial polymers as matrices. J. Pediatr Surg 23:3-9. 1988. Furthermore, the feasibility of using biodegradable polymers as delivery vehicles for urothelial cell transplantation has been demonstrated by studies showing that urothelial cells will adhere to synthetic polymers composed of polyglycolic acid and survive in vivo, as reported by Atala, et al., “Formation of urothelial structures in vivo from dissociated cells attached to biodegradable polymer scaffolds in vivo”, J. Urol., part 1, 148:658 (1992). However, this process is long and time consuming where a patient has to wait for at least eight weeks before the next implantation of a tissue engineered scaffold.
Tissue engineering based approaches, such as the cell culturing based technology (Oberpenning, et al. De novo reconstitution of a functional mammalian urinary bladder by tissue engineering. Nature Biotechnology Vol. 17 February 1999), has described the use of poly(glycolic acid) (PGA) scaffold for the reconstruction of the urinary bladder. Oberpenning, et al. compares the usefulness of synthetic polymer matrices in the absence (acellular group) and the presence of seeded cells (cellular group) for bladder reconstruction. In the study urothelial and smooth muscle cells were harvested, cultured and seeded on PGA nonwoven scaffold, were implanted in a beagle dog following partial cystectomy and evaluated over 11 months. The acellular group animal, at the end of the 6-month time frame, did not show any increase in the bladder capacity as compared to its baseline (precystectomy) volume and at the end of the 11 month time frame, the acellular group still did not reach its baseline capacity. Whereas in the cellular group at the end of 6 months, the bladder capacity almost reached its baseline capacity and at the end of 11 months the cellular group was able to approach and just surpass its precystectomy bladder capacity or volume. The results of the changes in the bladder capacity from this study are highlighted in FIG. 1. Some of the results from this study have been published in U.S. Pat. No. 6,576,019.
One significant limitation from the above study was that there was no significant increase in the bladder capacity over the precystectomy values, for both the groups at the end of 6 and 11 months. This could be a huge implication for neurogenic bladder patients, where there is always a need for an increased bladder capacity.
Therefore, there is a need in this art for novel scaffolds for correcting bladder defects, which do not require obtaining and implanting cells on the polymer scaffold.